Renal Tubular Function
Water and electrolytes freely filtered at glomerulus = similar content to plasma
Infants
Bulk movement in proximal tubule
Fine adjustments in distal tubule
Sodium resorption
Proximal tubule: 60% (cotransport with glucose or aa's)
Acending loop of Henle 25% (NaKCl transporter)
Distal tubule 15% (thiazide sensitive NaCl transporter)
Collecting tubule (epithelial Na transporter)
RDI Na 1-2 mEq/kg/day
Pseudohyponatremia
Na resorption controlled by
Baroreceptors in artia, carotid sinus, afferent arteriole
Chloride sensors in macula densa
renin-angiotensin-aldosterone axis (ATII increases prox tub resorp, Aldost dist tub resorp)
ADH: stimulates Na resorption and aquaporins allowing water resorption (H2O > Na = hyponatremia)
atrial natriuretic factor: increases Na excretion
Hypernatraemia
Diuretics impair sodium resorption
Potassium
Proximal tubule 100% resorption
excretion depended of secretion at collecting tubule (premoted by aldosterone)
Calcium
Resorbed by passive paracellular absorption, calcium channels and Ca transporters
Proximal tubule (70%)
ascending LOH (20%)
Distal tubule and CD (10%)
Resorption premoted by PTH, VitD (its main effect ie > GIT/Bone), thiazide diuretics, and low BP)
Phosphate
Actively absorbed in prox tubule
Absorption premoted by low BP, low PO4, GH
Excretion premoted by high BP, PTH
Magnesium
Resorption
Prox tubule (25%)
Ascending LOH (majority)
Dist Tubule (some)
Bicarbonate
Resorption (need to resorb before excreting H+)
H+ excretion facilitates HCO3 absorption as below
Prox tub (90%)
Distal (10%): thick ascending
Hydrogen
H2O in cell split to H+ and HCO3-
Carbonic anhydrase splits H2CO3 > H2O and CO2
CO2 diffuses back into cell, then combines with OH from initial split > HCO3
Renal tubular acidosis (normal anion gap metabolic acidosis)
type I: distal (impaired H+ secretion), urine pH >6.0, at risk of hypercalciuria
Type II: proximal (impaired HCO3 resorption), appropriate urine pH <5.5 as distal compensates, Ass: PO4HCO3 wasting
Type IV: hyperkalaemic (hypo/pseudohypoaldosteronism) aldosterone stimulated the H+APTase pump and K secretion
Urine anion gap (Na+K-Cl) confirms pH findings,<5.5 and AG - = proximal, >6.0 and AG+ = distal
Water
Normal losses: urine (60%), insens (~35%), stool (5%)
Insensible losses: Skin and Lung
Maintanance
Infants
- Reduced GFR
- Renal tubular immaturity
- Reduced responsiveness to antidiuretic hormone
Bulk movement in proximal tubule
Fine adjustments in distal tubule
Sodium resorption
Proximal tubule: 60% (cotransport with glucose or aa's)
Acending loop of Henle 25% (NaKCl transporter)
Distal tubule 15% (thiazide sensitive NaCl transporter)
Collecting tubule (epithelial Na transporter)
RDI Na 1-2 mEq/kg/day
Pseudohyponatremia
- hyperglycemia pulls H2O from cells (corr Na= measured Na + 0.3 (glucose - 5.5)
- hypertriglyceridaemia is miss read as H2O by analysers (lab will comment on lactescent/lipaemic ie milky serum)
- high protein
Na resorption controlled by
Baroreceptors in artia, carotid sinus, afferent arteriole
Chloride sensors in macula densa
renin-angiotensin-aldosterone axis (ATII increases prox tub resorp, Aldost dist tub resorp)
- Beta1adrenergic receptors stimulate renin secretion from juxtaglomerular cells (B-blocker)
- Renin
- CAH: cant make aldosterone > Na wasting
ADH: stimulates Na resorption and aquaporins allowing water resorption (H2O > Na = hyponatremia)
atrial natriuretic factor: increases Na excretion
Hypernatraemia
Diuretics impair sodium resorption
- PT: acetazolamide/mannitol
- Thick ascending LOH: Loop diuretics (Frusemide)
- DT: Thiazides (hydrochlorothiazide),
- Collecting Tub: K-sparing incuding aldosterone antagonists (Spironolactone)
Potassium
Proximal tubule 100% resorption
excretion depended of secretion at collecting tubule (premoted by aldosterone)
Calcium
Resorbed by passive paracellular absorption, calcium channels and Ca transporters
Proximal tubule (70%)
ascending LOH (20%)
Distal tubule and CD (10%)
Resorption premoted by PTH, VitD (its main effect ie > GIT/Bone), thiazide diuretics, and low BP)
- Williams Syndrome: hypercalciuria a feature ?high VitD ?increased sensitivity
Phosphate
Actively absorbed in prox tubule
Absorption premoted by low BP, low PO4, GH
Excretion premoted by high BP, PTH
Magnesium
Resorption
Prox tubule (25%)
Ascending LOH (majority)
Dist Tubule (some)
Bicarbonate
Resorption (need to resorb before excreting H+)
H+ excretion facilitates HCO3 absorption as below
Prox tub (90%)
Distal (10%): thick ascending
Hydrogen
H2O in cell split to H+ and HCO3-
- In PT: H+ secreted by Na/H exchanger in PT + ThickALOH
- In CT: H+ secreted by H+APTase
Carbonic anhydrase splits H2CO3 > H2O and CO2
CO2 diffuses back into cell, then combines with OH from initial split > HCO3
- In PT: Na/3HCO3 cotransporter shift out of cell to circulation
- In CT: Cl/3HCO3 exchanger shifts out of cell
Renal tubular acidosis (normal anion gap metabolic acidosis)
type I: distal (impaired H+ secretion), urine pH >6.0, at risk of hypercalciuria
Type II: proximal (impaired HCO3 resorption), appropriate urine pH <5.5 as distal compensates, Ass: PO4HCO3 wasting
- Fanconi syndrome: low molecular weight proteinuria, glycosuria, phosphaturia, aminoaciduria, and proximal RTA
Type IV: hyperkalaemic (hypo/pseudohypoaldosteronism) aldosterone stimulated the H+APTase pump and K secretion
Urine anion gap (Na+K-Cl) confirms pH findings,<5.5 and AG - = proximal, >6.0 and AG+ = distal
Water
Normal losses: urine (60%), insens (~35%), stool (5%)
Insensible losses: Skin and Lung
- 100-200ml/kg/day in VLBW prems
- <10kg 45ml/kg/day (40% of total in neonates)
- >10kg: 400 mL/m2/day (25% of total by adult)
- Skin loss > in PT/radiant heater/fever/burns/sweaty <in incubator
- fever = 10% increase for every degree above 38C (if persistant ie 1 hour of fever negligable)
- Lungs > in tachypnoea/tracheostomy < in humidified vent
- Other >third spacing, <hypothyroidism
- GIT > up in vom/NG asp (high in HCl) /diarrhoea (high in HCO3)
- Urine > polyuria
- Other > drain
- Gradient in medulla
- ADH (argenine vasopressin)
- produced in hypothalamus
- stored in the posterior pituitary
- osmoreceptors in hypothalamus detect increased osmolarity
- (severe low BP also triggers secretion)
- Binds ADH receptor AVPR2 in collecting tubule
- Receptor binding activates cAMP cascade (the major G-protein coupled receptor)
- Cascade causes preformed aquaporin 2 to insert in luminal membrane
- Water deprivation test = NBM and serial serum/urine osmolarity, vasopressin to differential cent from neph
Maintanance
- for oligo/anuria = insens + urine ml for ml (0.45%NaCl) to avoid overload
- for poly = insens + urine ml for ml (based on urine electrolytes) to avoid dehydration